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1.
Biochem Biophys Res Commun ; 529(2): 263-269, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32703421

RESUMO

The World Health Organization recently announced that pandemic status has been achieved for coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exponential increases in patient numbers have been reported around the world, along with proportional increases in the number of COVID-19-related deaths. The SARS-CoV-2 infection rate in a population is expected to be influenced by social practices, availability of vaccines or prophylactics, and the prevalence of susceptibility genes in the population. Previous work revealed that cellular uptake of SARS-CoV-2 requires Angiotensin Converting Enzyme 2 (ACE-2) and a cellular protease. The spike (S) protein on SARS-CoV-2 binds ACE-2, which functions as an entry receptor. Following receptor binding, transmembrane protease serine 2 (encoded by TMPRSS2) primes the S protein to allow cellular uptake. Therefore, individual expression of TMPRSS2 may be a crucial determinant of SARS-CoV-2 infection susceptibility. Here, we utilized multiple large genome databases, including the GTEx portal, SNP nexus, and Ensembl genome project, to identify gene expression profiles for TMPRSS2 and its important expression quantitative trait loci. Our results show that four variants (rs464397, rs469390, rs2070788 and rs383510) affect expression of TMPRSS2 in lung tissue. The allele frequency of each variant was then assessed in regional populations, including African, American, European, and three Asian cohorts (China, Japan and Taiwan). Interestingly, our data shows that TMPRSS2-upregulating variants are at higher frequencies in European and American populations than in the Asian populations, which implies that these populations might be relatively susceptible to SARS-CoV-2 infection.


Assuntos
Betacoronavirus/metabolismo , Regulação da Expressão Gênica/genética , Internacionalidade , Pulmão/metabolismo , Receptores Virais/genética , Serina Endopeptidases/genética , Ásia/etnologia , Estudos de Coortes , Europa (Continente)/etnologia , Frequência do Gene , Genética Populacional , Mapeamento Geográfico , Humanos , Especificidade de Órgãos/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Estados Unidos/etnologia , Regulação para Cima/genética
2.
Gene ; 758: 144944, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32628976

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The relentless spread and pathogenicity of the virus have become a global public health emergency. One of the striking features of this pandemic is the pronounced impact on specific regions and ethnic groups. In particular, compared with East Asia, where the virus first emerged, SARS-CoV-2 has caused high rates of morbidity and mortality in Europe. This has not been experienced in past global viral infections, such as influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is unique to SARS-CoV-2. For this reason, we investigated the involvement of genetic factors associated with SARS-CoV-2 infection with a focus on angiotensin-converting enzyme (ACE)-related genes, because ACE2 is a receptor for SARS-CoV-2. We found that the ACE1 II genotype frequency in a population was significantly negatively correlated with the number of SARS-CoV-2 cases. Similarly, the ACE1 II genotype was negatively correlated with the number of deaths due to SARS-CoV-2 infection. These data suggest that the ACE1 II genotype may influence the prevalence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.


Assuntos
Infecções por Coronavirus/mortalidade , Peptidil Dipeptidase A/genética , Pneumonia Viral/mortalidade , Ásia/epidemiologia , Ásia/etnologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/epidemiologia , Europa (Continente)/epidemiologia , Europa (Continente)/etnologia , Frequência do Gene/genética , Genótipo , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Risco , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Nature ; 583(7817): 572-577, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641827

RESUMO

The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas1-6, while critics have argued that these botanical dispersals need not have been human mediated7. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui)2. Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested8-12. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania13-15. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.


Assuntos
Fluxo Gênico/genética , Genoma Humano/genética , Migração Humana/história , Índios Centro-Americanos/genética , Índios Sul-Americanos/genética , Ilhas , Grupo com Ancestrais Oceânicos/genética , América Central/etnologia , Colômbia/etnologia , Europa (Continente)/etnologia , Genética Populacional , História Medieval , Humanos , Polimorfismo de Nucleotídeo Único/genética , Polinésia , América do Sul/etnologia , Fatores de Tempo
4.
Nature ; 582(7811): 240-245, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499647

RESUMO

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Aldeído-Desidrogenase Mitocondrial/genética , Alelos , Anquirinas/genética , Índice de Massa Corporal , Estudos de Casos e Controles , Europa (Continente)/etnologia , Proteínas do Olho/genética , Extremo Oriente/etnologia , Feminino , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio/genética , Humanos , Masculino , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/análise , Fatores de Transcrição/genética , Transcrição Genética
5.
Am J Hum Genet ; 106(6): 805-817, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32442408

RESUMO

Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze nine complex traits in individuals of East Asian and European ancestry, restricting to common SNPs (MAF > 5%), and find that most common causal SNPs are shared by both populations. Using the genome-wide estimates as priors in an empirical Bayes framework, we perform fine-mapping and observe that high-posterior SNPs (for both the population-specific and shared causal configurations) have highly correlated effects in East Asians and Europeans. In population-specific GWAS risk regions, we observe a 2.8× enrichment of shared high-posterior SNPs, suggesting that population-specific GWAS risk regions harbor shared causal SNPs that are undetected in the other GWASs due to differences in LD, allele frequencies, and/or sample size. Finally, we report enrichments of shared high-posterior SNPs in 53 tissue-specific functional categories and find evidence that SNP-heritability enrichments are driven largely by many low-effect common SNPs.


Assuntos
Grupos Étnicos/genética , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Teorema de Bayes , Europa (Continente)/etnologia , Extremo Oriente/etnologia , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Especificidade de Órgãos/genética
6.
Am J Hum Genet ; 106(6): 846-858, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32470372

RESUMO

The burden of several common diseases including obesity, diabetes, hypertension, asthma, and depression is increasing in most world populations. However, the mechanisms underlying the numerous epidemiological and genetic correlations among these disorders remain largely unknown. We investigated whether common polymorphic inversions underlie the shared genetic influence of these disorders. We performed an inversion association analysis including 21 inversions and 25 obesity-related traits on a total of 408,898 Europeans and validated the results in 67,299 independent individuals. Seven inversions were associated with multiple diseases while inversions at 8p23.1, 16p11.2, and 11q13.2 were strongly associated with the co-occurrence of obesity with other common diseases. Transcriptome analysis across numerous tissues revealed strong candidate genes for obesity-related traits. Analyses in human pancreatic islets indicated the potential mechanism of inversions in the susceptibility of diabetes by disrupting the cis-regulatory effect of SNPs from their target genes. Our data underscore the role of inversions as major genetic contributors to the joint susceptibility to common complex diseases.


Assuntos
Inversão Cromossômica/genética , Diabetes Mellitus/genética , Predisposição Genética para Doença , Hipertensão/genética , Obesidade/complicações , Obesidade/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 8/genética , Conjuntos de Dados como Assunto/normas , Diabetes Mellitus/patologia , Europa (Continente)/etnologia , Feminino , Perfilação da Expressão Gênica , Haplótipos , Humanos , Hipertensão/complicações , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Adulto Jovem
8.
J Neuroimmunol ; 341: 577166, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062178

RESUMO

BACKGROUND: Multiple sclerosis (MS) is recognized as the most prevalent chronic inflammatory neurological disorder diagnosed in young adults. Recent evidence suggests that the T244I polymorphism of the IL7Rα gene (rs6897932) May influence MS susceptibility; however, individual studies have provided conflicting and controversial results. Therefore, this meta-analysis was conducted to assess the association between the IL7R T244I polymorphism and the risk of MS. METHOD: An extensive search for published literature up to May 2019 was accomplished in the electronic databases, and 28 studies consisting of 16,260 MS patients and 18,335 controls were included. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to investigate the strength of association. RESULTS: The results of the present meta-analysis represented significant association between the IL7R T244I polymorphism and MS susceptibility. (recessive model: OR = 1.126, 95% CI 1.026-1.236, P = .012; dominant model: OR = 1.172, 95% CI 1.024-1.341, P = .021; homozygous model: OR = 1.213, 95% CI 1.038-1.417, P = .015; and allelic model: OR = 1.109, 95% CI 1.025-1.200, P = .010, respectively). In the subgroup analysis according to region, our findings showed significant association in Europe. However, no association was found in Middle East. CONCLUSION: The current meta-analysis demonstrated that the C allele of IL7R T244I polymorphism might be a risk factor for the MS susceptibility in Europe but not in Middle East.


Assuntos
Subunidade alfa de Receptor de Interleucina-7/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Alelos , Substituição de Aminoácidos , Intervalos de Confiança , Grupos de Populações Continentais/genética , Grupos Étnicos/genética , Europa (Continente)/etnologia , Predisposição Genética para Doença , Humanos , Subunidade alfa de Receptor de Interleucina-7/fisiologia , Oriente Médio/etnologia , Modelos Genéticos , Esclerose Múltipla/etnologia , Razão de Chances , Fatores de Risco
9.
Eur J Contracept Reprod Health Care ; 25(1): 20-27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31914332

RESUMO

Objectives: The aims of the study were to investigate foreign-born women's lifestyle and health before and during early pregnancy and compare them with those of Nordic-born women.Methods: Women recruited at antenatal clinics in Sweden answered a questionnaire in Swedish, English or Arabic or by telephone interview with an interpreter. Questions covered pregnancy planning and periconceptional lifestyle and health. The responses of women born in or outside Europe were compared with those of Nordic-born women. The impact of religiousness and integration on periconceptional lifestyle and health was also investigated.Results: Twelve percent of participants (N = 3389) were foreign-born (n = 414). Compared with Nordic women, European and non-European women consumed less alcohol before conception (respectively, adjusted odds ratio [aOR] 0.38; 95% confidence interval [CI] 0.24, 0.58 and aOR 0.14; 95% CI 0.10, 0.19) and during early pregnancy (respectively, aOR 0.61; 95% CI 0.40, 0.91 and aOR 0.20; 95% CI 0.14, 0.29). Non-European women used less tobacco and were less physically active, but body mass index (BMI) did not differ between groups. Self-perceived health, stress and anxiety during early pregnancy did not differ, but non-European women more often had depressive symptoms (aOR 1.67; 95% CI 1.12, 2.51). Non-European women's healthy lifestyle was associated with religiousness but not with the level of integration.Conclusions: Non-European women were overall less likely to engage in harmful lifestyle habits before and during early pregnancy but were more likely to suffer from depressive symptoms in comparison with Nordic women.


Assuntos
Serviços de Planejamento Familiar/estatística & dados numéricos , Estilo de Vida/etnologia , Cuidado Pré-Concepcional/estatística & dados numéricos , Gestantes/etnologia , Saúde da Mulher/etnologia , Adulto , Comparação Transcultural , Europa (Continente)/etnologia , Serviços de Planejamento Familiar/métodos , Feminino , Humanos , Cuidado Pré-Concepcional/métodos , Gravidez , Gestantes/psicologia , Inquéritos e Questionários , Suécia/etnologia
10.
PLoS One ; 14(12): e0225030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790415

RESUMO

The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Índios Norte-Americanos/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Adrenérgicos beta 2/genética , Adulto , África/etnologia , Alelos , Europa (Continente)/etnologia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , México/etnologia
11.
PLoS One ; 14(12): e0225212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790443

RESUMO

OBJECTIVE: While prediction models can estimate an infant's risk of developing obesity at a later point in early childhood, caregiver receptiveness to such information is largely unknown. We aimed to assess the acceptability of these models to New Zealand caregivers. METHODS: An anonymous questionnaire was distributed online. The questionnaire consisted of multiple choice and Likert scale questions. Respondents were parents, caregivers, and grandparents of children aged ≤5 years. RESULTS: 1,934 questionnaires were analysed. Responses were received from caregivers of various ethnicities and levels of education. Nearly two-thirds (62.1%) of respondents would "definitely" or "probably" want to hear if their infant was at risk of early childhood obesity, although "worried" (77.0%) and "upset" (53.0%) were the most frequently anticipated responses to such information. With lower mean scores reflecting higher levels of acceptance, grandparents (mean score = 1.67) were more receptive than parents (2.10; p = 0.0002) and other caregivers (2.13; p = 0.021); males (1.83) were more receptive than females (2.11; p = 0.005); and Asian respondents (1.68) were more receptive than those of European (2.05; p = 0.003), Maori (2.11; p = 0.002), or Pacific (2.03; p = 0.042) ethnicities. There were no differences in acceptance according to socioeconomic status, levels of education, or other ethnicities. CONCLUSIONS: Almost two-thirds of respondents were receptive to communication regarding their infant's risk of childhood obesity. While our results must be interpreted with some caution due to their hypothetical nature, findings suggest that if delivered in a sensitive manner to minimise caregiver distress, early childhood obesity risk prediction could be a useful tool to inform interventions to reduce childhood obesity in New Zealand.


Assuntos
Comunicação , Obesidade Pediátrica/epidemiologia , Adolescente , Adulto , Ásia/etnologia , Atitude Frente a Saúde/etnologia , Cuidadores/psicologia , Pré-Escolar , Europa (Continente)/etnologia , Retroalimentação , Feminino , Previsões , Avós/psicologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Nova Zelândia/etnologia , Pais/psicologia , Obesidade Pediátrica/etnologia , Obesidade Pediátrica/prevenção & controle , Risco , Inquéritos e Questionários , Adulto Jovem
12.
Popul Health Metr ; 17(1): 14, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675961

RESUMO

BACKGROUND: Many studies on migrant health have focused on aspects of morbidity and mortality, but very few approach the relevant issues of migrants' health considering behavioral risk factors. Previous studies have often been limited methodologically because of sample size or lack of information on migrant country of origin. Information about risk factors is fundamental to direct any intervention, particularly with regard to non-communicable diseases that are leading causes of death and disease. Thus, the main focus of our analysis is the influence of country of origin and the assimilation process. METHOD: Utilizing a surveillance system that has been collecting over 30,000 interviews a year in Italy since 2008, we have studied migrants' attitudes and behaviors by country of origin and by length of stay. Given 6 years of observation, we have obtained and analyzed 228,201 interviews of which over 9000 were migrants. RESULTS: While migrants overall present similar conditions to native-born Italians, major differences appear when country of origin or length of stay is considered. Subgroups of migrants present substantially different behaviors, some much better than native-born Italians, some worse. However, integration processes generally produce a convergence towards the behavioral prevalence observed for native-born Italians. CONCLUSIONS: Health programs should consider the diversity of the growing migrant population: data and analyses are needed to support appropriate policies. Many migrants' subgroups arrive with healthier behaviors than those of their adopted country. However, they are likely to have a less favorable social position in their destination countries that could lead to a change towards less healthy behaviors. Interventions capable of identifying this tendency could produce significant better health for this important part of the future (multicultural) populations.


Assuntos
Aculturação , Emigrantes e Imigrantes , Comportamentos Relacionados com a Saúde , Nível de Saúde , Adolescente , Adulto , África ao Sul do Saara/etnologia , África do Norte/etnologia , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Ásia/etnologia , Bebedeira/epidemiologia , Fumar Cigarros/epidemiologia , Depressão/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Europa (Continente)/etnologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Questionário de Saúde do Paciente , Refugiados , Fatores de Risco , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
15.
Hum Immunol ; 80(10): 807-822, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31345698

RESUMO

The human leukocyte antigen (HLA) genes are extremely polymorphic and are useful molecular markers to make inferences about human population history. However, the accuracy of the estimation of genetic diversity at HLA loci very much depends on the technology used to characterize HLA alleles; high-resolution genotyping of long-range HLA gene products improves the assessment of HLA population diversity as well as other population parameters compared to lower resolution typing methods. In this study we examined allelic and haplotype HLA diversity in a large healthy European American population sourced from the UCSF-DNA bank. A high-resolution next-generation sequencing method was applied to define non-ambiguous 3- and 4-field alleles at the HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 loci in samples provided by 2248 unrelated individuals. A number of population parameters were examined including balancing selection and various measurements of linkage disequilibrium were calculated. There were no detectable deviations from Hardy-Weinberg proportions at HLA-A, HLA-DRB1, HLA-DQA1 and HLA-DQB1. For the remaining loci moderate and significant deviations were detected at HLA-C, HLA-B, HLA-DRB3/4/5, HLA-DPA1 and HLA-DPB1 loci mostly from population substructures. Unique 4-field associations were observed among alleles at 2 loci and haplotypes extending large intervals that were not apparent in results obtained using testing methodologies with limited sequence coverage and phasing. The high diversity at HLA-DPA1 results from detection of intron variants of otherwise well conserved protein sequences. It may be speculated that divergence in exon sequences may be negatively selected. Our data provides a valuable reference source for future population studies that may allow for precise fine mapping of coding and non-coding sequences determining disease susceptibility and allo-immunogenicity.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene/genética , Genética Populacional/métodos , Antígenos HLA/genética , Haplótipos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Coortes , Europa (Continente)/etnologia , Grupo com Ancestrais do Continente Europeu/etnologia , Feminino , Loci Gênicos/genética , Teste de Histocompatibilidade , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
17.
J Stud Alcohol Drugs ; 80(3): 319-330, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31250797

RESUMO

OBJECTIVE: The opioid epidemic in the United States has led to unprecedented increases in morbidity and mortality, posing a serious public health crisis. Although twin and family studies, as well as genome-wide association studies (GWAS), all identify significant genetic factors contributing to opioid dependence, no studies to date have estimated marker-based heritability estimates of opioid dependence. The goal of the current study was to use a large, genetically imputed, case/control sample of 4,064 participants (after quality control and imputation) with genome-wide data to estimate the unbiased heritability tagged by single nucleotide polymorphisms (SNPs). METHOD: Study data were part of the Genome-wide Study of Heroin Dependence obtained via the Database for Genotypes and Phenotypes (dbGaP). Genomic-Relatedness-Matrix Restricted Maximum Likelihood with adjustment for minor allele frequency (MAF) and linkage disequilibrium (LD; GREML-LDMS) was used to determine the variation in opioid dependence attributable to common SNPs from imputed data. Mixed linear models were used in an exploratory GWAS to assess effects of single SNPs. RESULTS: At least 45% of the variance in opioid dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was attributable to common SNPs, after stratifying to account for differences in MAF and LD across the genome. Most of the genetic variance was tagged by SNPs in the 1%-9% MAF range and in low LD with other SNPs in the region. Two markers in LOC101927293 survived multiple-testing correction (i.e., q value < .05). CONCLUSIONS: Nearly half of the variation in opioid dependence can be attributed to common SNPs. Most of this variation is due to rare variants in low LD with other markers in the region.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Europa (Continente)/etnologia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
PLoS One ; 14(6): e0218706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233524

RESUMO

Late diagnosis and treatment may increase morbidity and mortality among persons with hepatitis C virus (HCV) infection. We included all participants of the Swiss Hepatitis C Cohort Study (SCCS). We used unadjusted and adjusted logistic and Cox regressions to determine the association between the geographic origin of the participants and the following outcomes: antiviral treatment status; sustained virologic response; cirrhosis at enrolment; incident cirrhosis; loss to follow-up (LTFU); and mortality. The analyses were adjusted for sex, baseline age, education, source of income, alcohol consumption, injection drug use (IDU), HCV genotype, HIV or HBV coinfection, duration of HCV infection, time since enrolment, cirrhosis, (type of) HCV treatment, and centre at enrolment. Among 5,356 persons, 1,752 (32.7%) were foreign-born. IDU was more common among Swiss- (64.1%) than foreign-born (36.6%) persons. Cirrhosis at enrolment was more frequent among foreign- than Swiss-born persons, reflecting the high frequency of cirrhosis among Italian-born persons who acquired HCV between 1950 and 1970 in Italian healthcare settings. Although antiviral treatment coverage was similar, the sustained viral response rate was increased and the mortality was lower among foreign-vs. Swiss-born persons, with the lowest mortality in persons from Asia/Oceania. LTFU was more frequent in persons from Germany, Eastern and Southern Europe, and the Americas. In conclusion, in Switzerland, a country with universal healthcare, geographic origin had no influence on hepatitis C treatment access, and the better treatment outcomes among foreign-born persons were likely explained by their lower prevalence of IDU and alcohol consumption than among Swiss-born persons.


Assuntos
Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , América/etnologia , Antivirais/uso terapêutico , Ásia/etnologia , Estudos de Coortes , Emigrantes e Imigrantes , Europa (Continente)/etnologia , Feminino , Alemanha/etnologia , Acesso aos Serviços de Saúde , Hepatite C/tratamento farmacológico , Hepatite C/mortalidade , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Oceania/etnologia , Resposta Viral Sustentada , Suíça/epidemiologia , Resultado do Tratamento , Adulto Jovem
19.
BMC Public Health ; 19(1): 796, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226971

RESUMO

BACKGROUND: This study assesses how tuberculosis (TB) screening is perceived by immigrants in Norway. Screening is mandatory for people arriving from high incidence countries. To attend screening, immigrants have to contact the health system after receiving an invitation by letter. The proportion of non-attenders is not known, and there are no sanctions for not attending. Generally, only persons who test positive receive test results. The study explores users' experiences, attitudes and motivations for attending or not attending TB screening, and perceived barriers and enablers. METHODS: We conducted six focus group discussions and three individual interviews with 34 people from 16 countries in Africa, Asia and Europe. Interviews were recorded and transcribed, and data was coded following a general inductive approach: All transcribed text data was closely read through, salient themes were identified and categories were created and labelled. The data was read through several times and the category system was subsequently revised. RESULTS: Most appreciated the opportunity to be tested for a severe disease and were generally positive towards the healthcare system. At the same time, many were uncomfortable with screening, particularly due to the fear and stigma attached to TB. All experienced practical problems related to language, information, and accessing facilities. Having to ask others for help made them feel dependent and vulnerable. Positive and negative attitudes simultaneously created ambivalence. Many wanted "structuring measures" like sanctions to help attendance. Many said that not receiving results left them feeling anxious. CONCLUSIONS: In order to adapt the system and improve trust and patient uptake, all aspects of the screening should be taken into account. Ambivalence towards screening probably has a negative impact on screening uptake and should be sought reduced. A combination of ambivalence and a wish for "structuring measures" leads the authors to conclude that mandatory screening is a reasonable measure. However, since mandatory screening negatively impacts patient autonomy, and because of fear, stigma and practical problems, the health system should empower users by improving communication and access to services. In addition, it is recommended that negative test results are also communicated to the users.


Assuntos
Atitude Frente a Saúde , Emigrantes e Imigrantes/psicologia , Programas de Rastreamento/psicologia , Tuberculose/prevenção & controle , Adulto , África/etnologia , Ásia/etnologia , Emigrantes e Imigrantes/estatística & dados numéricos , Europa (Continente)/etnologia , Feminino , Grupos Focais , Acesso aos Serviços de Saúde , Humanos , Masculino , Motivação , Noruega , Pesquisa Qualitativa
20.
Nature ; 570(7760): 182-188, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31168093

RESUMO

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.


Assuntos
Genoma Humano/genética , Migração Humana/história , Ásia/etnologia , DNA Antigo/análise , Europa (Continente)/etnologia , Pool Gênico , Haplótipos , História do Século XV , História Antiga , História Medieval , Humanos , Índios Norte-Americanos , Masculino , Sibéria/etnologia
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